Journal Article

Genetic Variants of Complement Factor H Y402H (rs1061170), C2 R102G (rs2230199), and C3 E318D (rs9332739) and Response to Intravitreal Anti-VEGF Treatment in Patients with Exudative Age-Related Macular Degeneration

Żuber-Łaskawiec, Katarzyna, Sanak, Marek, Romanowska-Dixon, Bożena, Kubicka-Trząska, Agnieszka, Dziedzina, Sylwia, Karska-Basta, Izabella

2022

Overview

Background and Objectives: To assess the association between the single nucleotide polymorphisms (SNPs) in the genes encoding complement factors CFH, C2, and C3 (Y402H rs1061170, R102G rs2230199, and E318D rs9332739, respectively) and response to intravitreal anti-vascular endothelial growth factor (VEGF) therapy in patients with exudative age-related macular degeneration (AMD). Materials and Methods: The study included 111 patients with exudative AMD treated with intravitreal bevacizumab or ranibizumab injections. Response to therapy was assessed on the basis of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measured every 4 weeks for 12 months. The control group included 58 individuals without AMD. The SNPs were genotyped by a real-time polymerase chain reaction in genomic DNA isolated from peripheral blood samples. Results: The CC genotype in SNP rs1061170 of the CFH gene was more frequent in patients with AMD than in controls (p = 0.0058). It was also more common among the 28 patients (25.2%) with poor response to therapy compared with good responders (p = 0.0002). Poor responders, especially those without this genotype, benefited from switching to another anti-VEGF drug. At the last follow-up assessment, carriers of this genotype had significantly worse BCVA (p = 0.0350) and greater CRT (p = 0.0168) than noncarriers. TT genotype carriers showed improved BCVA (p = 0.0467) and reduced CRT compared with CC and CT genotype carriers (p = 0.0194). No associations with AMD or anti-VEGF therapy outcomes for SNP rs9332739 in the C2 gene and SNP rs2230199 in the C3 gene were found. Conclusions: The CC genotype for SNP rs1061170 in the CFH gene was associated with AMD in our population. Additionally, it promoted a poor response to anti-VEGF therapy. On the other hand, TT genotype carriers showed better functional and anatomical response to anti-VEGF therapy at 12 months than carriers of the other genotypes for this SNP.

• Publisher: MDPI AG,MDPI
• Subject: age-related macular degeneration / anti-VEGF therapy / Bevacizumab - pharmacology / Bevacizumab - therapeutic use / Complement Factor H - genetics / Complement Factor H - metabolism / Complement Factor H - therapeutic use / complement system / Family medical history / Genetic disorders / Genotype / Humans / Macular degeneration / Macular Degeneration - drug therapy / Macular Degeneration - genetics / Medical imaging / Monoclonal antibodies / Older people / Polymerase chain reaction / Polymorphism, Single Nucleotide - genetics / Proteins / single nucleotide polymorphism / switching therapy / Vascular endothelial growth factor